Analysis of morphological changes after facial massage by a novel approach using three-dimensional computed tomography.

BACKGROUND/PURPOSE: Photograph-based visual scoring has been used for evaluation of facial morphological changes. Here, we describe a three-dimensional computed tomography (3D-CT) method for objective analysis of facial and intra-facial (subcutaneous) changes. The effects of facial massage were examined using both methods. METHODS: Subjects were 12 healthy female volunteers without facial scars or deformation (age 30-54 years, mean 39.4 years). Photograph-based scoring of massage-induced morphological changes was done at the nasolabial folds, upper, lower and lateral cheeks and lower eyelids. For 3D-CT evaluation, the virtual center axis (VCA) was set as the cranio-caudal longitudinal line, and the VCA-skin surface distances (VSDs) were measured. Massage-induced changes of VSD were calculated (facial massage-induced change rate, FMCR). Intra-facial (subcutaneous) changes were also evaluated. RESULTS: Photograph-based scoring revealed marked morphological changes of the nasolabial folds after facial massage, and changes of the lower, upper and lateral cheeks and lower eyelid were also observed in more than half of the subjects. FMCR values were significantly changed in the paranasal area, nasolabial fold area and cranial part of the mandibular area. Photograph-based scores at the lower cheek and lower eyelid were well correlated with FMCR in the inferior part of the nasolabial fold and the mandibular area, respectively. Massage-induced changes of subcutaneous fat tissues and facial expression muscles were also apparent on CT images. CONCLUSION: 3D-CT imaging is useful for objective evaluation of the effects of facial massage, including anatomical changes in subcutaneous structures.

Dermal anchoring structures: convex matrix structures at the bottom of the dermal layer that contribute to the maintenance of facial skin morphology.

BACKGROUND/PURPOSE: Facial skin must be linked to underlying structures to maintain facial morphology and prevent sagging, but the mechanism of facial skin retention is largely unknown. We aimed to elucidate this mechanism. METHODS: Twenty-two cheek skin specimens (age range: 10s-60s, both genders) were observed histologically. And 30 cheek of healthy Japanese volunteers (age range: 30s-50s, female) was photographed and the severity of sagging was graded. Dermal layer morphology was observed non-invasively with ultrasound. Skin-retaining force was measured with a Cutometer MPA 580(®) , and sagging severity was evaluated by grading criteria. RESULTS: Histological observation revealed characteristic convex structures at the bottom of the dermal layer. Non-invasive study showed that the depth of the convex structures, measured by ultrasonography, was significantly negatively related to the ratio of viscoelastic to elastic distention (Uv/Ue) and positively related to the ratio of elastic recovery to total deformation (Ur/Uf) at the cheek of female volunteers, measured by cutometer. It was also negatively related to sagging severity. Further, Ur/Uf was negatively and Uv/Ue was positively related to sagging severity. CONCLUSION: Characteristic convex structures at the bottom of the dermal layer serve as anchoring structures to maintain skin morphology.

Effectiveness of female community health volunteers in the detection and management of low-birth-weight in Nepal.

INTRODCTION: Low birth weight (LBW) is a major risk factor for neonatal death. However, most neonates in low-income countries are not weighed at birth. This results in many LBW infants being overlooked. Female community health volunteers (FCHVs) in Nepal are non-health professionals who are living in local communities and have already worked in a field of reproductive and child health under the government of Nepal for more than 20 years. The effectiveness of involving FCHVs to detect LBW infants and to initiate prompt action for their care was studied in rural areas of Nepal. METHODS: FCHVs were tasked with weighing all neonates born in selected areas using color-coded spring scales. Supervisors repeated each weighing using electronic scales as the gold standard comparator. Data on the relative birth sizes of the infants, as assessed by their mothers, were also collected and compared with the measured weights. Each of the 205 FCHVs involved in the study was asked about the steps that she would take when she came across a LBW infant, and knowledge of zeroing a spring scale was also assessed through individual interviews. The effect of the background social characteristics of the FCHVs on their performance was examined by logistic regression. This study was nested within a community-based neonatal sepsis-management intervention surveillance system, which facilitated an assessment of the performance of the FCHVs in weighing neonates, coverage of FCHVs' visits, and weighing of babies through maternal interviews. RESULTS: A total of 462 babies were weighed, using both spring scales and electronic scales, within 72 hours of birth. The prevalence of LBW, as assessed by the gold standard method, was 28%. The sensitivity of detection of LBW by FCHVs was 89%, whereas the sensitivity of the mothers' perception of size at birth was only 40%. Of the 205 FCHVs participating in the study, 70% of FCHVs understood what they should do when they identified LBW and very low birth weight (VLBW) infants. Ninety-six per cent could describe how to zero a scale and approximately 50% could do it correctly. Seventy-seven per cent of FCHVs weighed infants at least once during the study period, and 19 of them (12%) miscategorized infant weights. Differences were not detected between the background social characteristics of FCHVs who miscategorized infants and those who did not. On the basis of maternal reporting, 67% of FCHVs who visited infants had weighed them. CONCLUSIONS: FCHVs are able to correctly identify LBW and VLBW infants using spring scales and describe the correct steps to take after identification of these infants. Use of FCHVs as newborn care providers allows for utilization of their logistical, geographical, and cultural strengths, particularly a high level of access to neonates, that can complement the Nepalese healthcare system. Providing additional training to and increasing supervision of local FCHVs regarding birth weight measurement will increase the identification of high-risk neonates in resource-limited settings.

International models of investigator-initiated trials: implications for Japan.

BACKGROUND: Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials. MATERIALS: In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world. RESULTS: In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval. CONCLUSIONS: To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval.

Body cavity fluid can induce epithelial and mesothelial differentiation from CD34 positive peripheral blood stem cells in vitro.

OBJECTIVE: Primary culture of CD34 positive stem cells collected from human peripheral blood was performed with and without supplementation with concentrated ascitic fluid; morphological and immunocytochemical pictures of cultured cells were taken chronologically and compared. METHODS: CD34-positive stem cells collected from peripheral blood were cultured for 1, 24 and 48 hours. Concentrated ascitic fluid was added to the plates for the 24-and 48-hour cultures. For immunocytochemical studies, CD34, AE1/AE3, Ber-Ep4 (EA), EMA, EGFR, CD31, CA125 and D2-40 monoclonal antibodies were used. RESULTS: After culture, small round cells with naked nuclei began to enlarge and to exhibit various changes in the cytoplasm and nucleus. Supplementation with concentrated body cavity fluid enhanced these changes. CD34-positive cells with small round cell features were detected 1 hour after culture and these had no epithelial or mesothelial markers. After 24 hours, CD34-positive cells had disappeared and cells weakly positive for EGFR, EMA, CA125 and D2-40 were detected. Cells with strong and moderate positive reactions for EGFR, AE1/AE3, EA, EMA, D2-40 and CA125 were detected after 48 hours. Supplementation with concentrated body cavity fluid increased the intensity and number of positive cells for these markers compared with the control group. The positive reaction, not only for the epithelial markers such as EGFR and AE1/AE3, but also for mesothelial markers such as CA125 and D2-40, was found to be increased in small numbers of cells in direct proportion to the duration of the primary culture of the peripheral blood cells. CD31, characteristically expressed in endothelial cells, was negative in the cultured cells. CONCLUSION: Supplementation of peripheral blood CD34-positive stem cells with body cavity fluid in vitro enhanced their differentiation toward cells of an epithelial or mesothelial phenotype, concomitant with loss of immunoreactivity for CD34. It is assumed that the routine cytological observation of cells obtained from body cavity fluid might cause possible cytomorphological and immunophenotypical changes due to the action of the growth factors contained in the body cavity fluid.

Sagging of the cheek is related to skin elasticity, fat mass and mimetic muscle function.

BACKGROUND/PURPOSE: Facial sagging is associated with aging, although the mechanism remains unclear. The aim of this study was to investigate the mechanism of facial sagging by examining the relationship of sagging severity to changes of skin elasticity, fat mass and facial muscle function at the cheek. METHODS: Faces of 108 healthy Japanese female volunteers, aged 20-60 years were photographed at an angle of 45 degrees . Standard scores of sagging severity were established by analyzing the photographs. We examined the correlations of scored sagging levels with skin elasticity measured with a Cutometer MPA 580, fat content estimated by bioelectrical impedance analysis and facial muscle function (lip sealing force and occlusal force) in middle-aged female volunteers (30-40 years) with a wide range of sagging scores. RESULTS: Because the upper, lower and lateral areas in the cheek may show severe sagging, a six-grade score of sagging severity was separately established for each area. Each score was significantly correlated positively with age (20-60 years). In middle-aged volunteers, the sagging scores in all three areas of the cheek were significantly and negatively associated with skin elasticity. Body fat percentage was significantly and positively correlated with the sagging scores in the lower and lateral areas, although the correlation was only weakly positive in the upper area. Mimetic muscle function, measured in terms of lip sealing pressure, was significantly and negatively correlated with the sagging score only at the upper area of the cheek, but masticatory muscle function, measured in terms of occlusal force pressure, was not associated with the sagging score. CONCLUSIONS: Sagging may be associated with the reduction of skin elasticity and mimetic muscle function and increase of fat mass, but the relationships are different in different areas of the cheek.

Difference in the odor concentrations measured by the triangle odor bag method and dynamic olfactometry.

'The triangle odor bag method', which has been adopted for the offensive odor control law in Japan, and the dynamic olfactometry defined by EN 13725 have been compared. The odor concentration measured by the triangle odor bag method tends to be higher than that of the dynamic olfactometry in the forced choice mode, while well agreed in the Yes/No mode olfactometry when the panel is the same. The difference can be minimized by applying the panel selection criterion of EN13725 to the triangle odor bag method. The European panel selection test is useful to negate the difference in the measurement equipments although the criteria seem to be strict considering the individual threshold data of n-butanol.

Plasmin induces degradation and dysfunction of laminin 332 (laminin 5) and impaired assembly of basement membrane at the dermal-epidermal junction.

BACKGROUND: The epidermal basement membrane (BM), located at the dermal-epidermal junction (DEJ), plays important roles not only in adhesion between epidermis and dermis, but also in controlling skin functions. In sun-exposed skin, the BM becomes disrupted and multilayered. In order to explore the impairment of BM assembly, we have used a skin-equivalent (SE) as a model of BM damage and previously clarified the involvement of matrix metalloproteinases (MMPs) in impairment of BM assembly. OBJECTIVES: In this work, we examined the role of urokinase-type plasminogen activator (uPA) and plasmin in impairment of BM assembly at the DEJ by using the SE, as ultraviolet irradiation to the skin increases uPA as well as MMPs. METHODS: SEs were used as a model of formation and damage of BM. Human uPA was detected by enzyme-linked immunosorbent assay and zymography, and gelatinases such as MMP-2 and MMP-9 were detected by zymography. Human plasminogen was added at 0.06 micromol L(-1) (about 3% of plasma level) to increase plasmin to a pathological level. N-terminal peptide sequence analysis of plasmin-treated laminin 332 was carried out to identify alpha3, beta3 and gamma2 chains of laminin 332 and their cleavage sites of each chain. Plasmin-treated laminin 332 was analysed in keratinocyte adhesion activity and binding to type VII collagen. RESULTS: Human uPA was detected in addition to MMP-2 and MMP-9, in conditioned medium of SE. Although the BM was well organized in the presence of an MMP inhibitor alone, the activated plasmin disorganized the BM even in the presence of the inhibitor. The impairment of BM assembly made the epidermis thinner as compared with that of a control cultured in the presence of MMP inhibitor, indicating that the BM affects the polarity and differentiation of the epidermis. The addition of aprotinin, a serine proteinase inhibitor, and tranexamic acid, a uPA-plasmin inhibitor, inhibited the plasmin-induced impairment of BM assembly and facilitated BM reorganization, thereby improving the epidermal structure. N-terminal peptide sequence analysis of plasmin-treated laminin 332 revealed the removal of a 5- or 10-kDa fragment, including the cell adhesion region, from the G3 domain of the alpha3 chain, and the LN domain, which binds to the noncollagenous 1 domain in type VII collagen, from the beta3 chain. Plasmin-treated laminin 332 showed lower keratinocyte adhesion activity and reduced binding to type VII collagen. CONCLUSIONS: These results suggest that uPA and plasmin are involved in the impairment of BM assembly and epidermal differentiation, and that these effects arise at least partly through direct degradation of laminin 332.

Advanced glycation end products increase retinal vascular endothelial growth factor expression.

Advanced glycation end products (AGEs) are linked with the development of diabetic retinopathy; however, the pathogenic mechanisms are poorly defined. Vascular endothelial growth factor (VEGF) levels are increased in ischemic and nonischemic diabetic retina, and VEGF is required for the development of retinal and iris neovascularization. Moreover, VEGF alone can induce much of the concomitant pathology of diabetic retinopathy. In this study, we found that AGEs increased VEGF mRNA levels in the ganglion, inner nuclear, and retinal pigment epithelial (RPE) cell layers of the rat retina. In vitro, AGEs increased VEGF mRNA and secreted protein in human RPE and bovine vascular smooth muscle cells. The AGE-induced increases in VEGF expression were dose- and time-dependent, inhibited by antioxidants, and additive with hypoxia. Use of an anti-VEGF antibody blocked the capillary endothelial cell proliferation induced by the conditioned media of AGE-treated cells. AGEs may participate in the pathogenesis of diabetic retinopathy through their ability to increase retinal VEGF gene expression.

Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo.

Elevated vascular endothelial growth factor (VEGF) levels are required for ocular and tumor angiogenesis in animal models. Ischemic hypoxia is strongly correlated with increased VEGF expression in these systems and is considered a physiologically relevant stimulus. Because ischemic hypoxia is often followed by reperfusion and reactive oxygen intermediate (ROI) generation, we examined the potential role of ROI in the control of VEGF gene expression. Human retinal pigment epithelial cells exposed to superoxide or hydrogen peroxide rapidly increased VEGF mRNA levels. Superoxide-associated mRNA increases were dose dependent, blocked by antioxidants, and associated with elevated VEGF protein levels in conditioned media. Increases in VEGF mRNA levels were also observed in cultured human melanoma and rat glioblastoma cells with superoxide or hydrogen peroxide. Cycloheximide prevented the ROI-associated increases in VEGF mRNA. Transcriptional inhibition with actinomycin D revealed an inducible increase in VEGF mRNA half-life, but nuclear run-on experiments showed no increase in VEGF transcriptional rate. Reoxygenation of human retinal pigment epithelial cells in vitro and ocular reperfusion in vivo increased retinal VEGF mRNA levels. Antioxidants prevented the reperfusion-associated VEGF mRNA increases in retina. We conclude that ROIs increase VEGF gene expression in vitro and during the reperfusion of ischemic retina in vivo. The ROI-associated increases are mediated largely through increases in VEGF mRNA stability.

Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis.

Proximal renal tubular acidosis associated with ocular abnormalities such as band keratopathy, glaucoma, and cataracts is caused by mutations in the Na(+)-HCO(3)(-) cotransporter (NBC-1). However, the mechanism by which NBC-1 inactivation leads to such ocular abnormalities remains to be elucidated. By immunological analysis of human and rat eyes, we demonstrate that both kidney type (kNBC-1) and pancreatic type (pNBC-1) transporters are present in the corneal endothelium, trabecular meshwork, ciliary epithelium, and lens epithelium. In the human lens epithelial (HLE) cells, RT-PCR detected mRNAs of both kNBC-1 and pNBC-1. Although a Na(+)-HCO(3)-cotransport activity has not been detected in mammalian lens epithelia, cell pH (pH(i)) measurements revealed the presence of Cl(-)-independent, electrogenic Na(+)-HCO(3)-cotransport activity in HLE cells. In addition, up to 80% of amiloride-insensitive pH(i) recovery from acid load in the presence of HCO(3)(-)/CO(2) was inhibited by adenovirus-mediated transfer of a specific hammerhead ribozyme against NBC-1, consistent with a major role of NBC-1 in overall HCO(3)-transport by the lens epithelium. These results indicate that the normal transport activity of NBC-1 is indispensable not only for the maintenance of corneal and lenticular transparency but also for the regulation of aqueous humor outflow.

Advanced glycation end product deposits in climatic droplet keratopathy.

BACKGROUND: Climatic droplet keratopathy (CDK), known as spheroid degeneration of the cornea, is one of the most frequent degenerative corneal disorders affecting visual function. However, the histochemical nature of the deposits seen in CDK is still unclear. AIM: To investigate the pathogenesis of CDK, we investigated the immunohistochemical localisation of advanced glycation end products (AGEs) in surgical specimens of CDK. METHODS: Immunohistochemical localisation of N(epsilon)-(carboxymethyl)-l-lysine (CML), N(epsilon)-(carboxyethyl)-l-lysine (CEL), pyrraline, pentosidine and imidazolone was examined in three corneas with CDK, six corneas with bullous keratopathy and three corneas without any corneal diseases. RESULTS: In all the specimens with CDK, immunoreactivity was strong in CML, moderate in pyrraline and pentosidine, and weak in imidazolone. Immunoreactivity was absent in CEL. In contrast, no immunoreactivity to CML, pyrraline, pentosidine, imidazolone or CEL was detected in corneas with bullous keratopathy, or in corneas without any corneal diseases. CONCLUSIONS: CDK is caused by an aggregation of AGE-modified proteins. The result is consistent with etiological findings that ultraviolet irradiation and ageing, both of which are accelerators of AGE formation, are closely related to the development of CDK.

Analysis of c-KIT exon 11 mutations in canine gastrointestinal stromal tumours.

The aim of this study was to determine the type and frequency of c-KIT exon 11 mutations in canine gastrointestinal stromal tumours (GISTs) and investigate the association between the c-KIT mutation status and KIT immunohistochemical staining pattern. Mutations in exon 11 of c-KIT were examined in 46 formalin-fixed paraffin-embedded canine GISTs using PCR of genomic DNA and reverse transcription-PCR (RT-PCR) of cDNA. Exon 11 c-KIT mutations were detected in 15/46 (32.6%) cases by conventional PCR and 34/46 (73.9%) cases by RT-PCR; the mutation detection rate was significantly higher for RT-PCR (P = 0.004, Fisher's exact test). Ten different mutations, including deletion, internal tandem duplication and point mutations, were identified by RT-PCR. Immunohistochemistry was performed using an anti-KIT antibody; diffuse KIT staining was detected in the tumour cell cytoplasm in 32/46 (69.6%) cases and partial or stippled cytoplasmic staining of KIT was observed in 14/46 (30.4%) cases. Neither pattern was significantly associated with c-KIT exon 11 mutation status (P = 1.000, chi-square test). These data indicate that c-KIT exon 11 mutations occur frequently in canine GISTs, similar to human GISTs; however, there is no association between c-KIT mutations and the KIT expression pattern in canine GISTs. This study suggests that RT-PCR is more sensitive than conventional PCR for the detection of c-KIT mutations in canine GISTs.

Normal developing rat brain expresses a platelet-derived growth factor B chain (c-sis) mRNA truncated at the 5' end.

The 5' untranslated sequence (5' UTS) of platelet-derived growth factor B (PDGF-B/c-sis) mRNA is highly preserved through evolution, and inhibits translation of downstream coding sequences. In this study, using Northern analysis we identified two PDGF-B/c-sis mRNAs (3.5 kb and 2.6 kb) expressed in normal developing rat brain. In contrast to the constitutive expression of 3.5 kb mRNA, the expression of 2.6 kb mRNA increased markedly in accordance with those stages of brain development at which we had previously demonstrated an increased immunoreactivity for PDGF-B/c-SIS in neurons (Sasahara et al., 1992). By PCR cloning and the RNase protection assay, we determined the complete sequence of rat PDGF-B/c-sis, and found that the 2.6 kb transcript was a form of the 3.5 kb message truncated at the 5' end, and that the predominant 2.6 kb mRNA commenced 15 nt upstream of the signal peptide. Accordingly, it is suggested that the truncation of 5' UTS contributes to the expression of PDGF-B/c-SIS protein in the CNS. Lack of translational inhibitory 5' UTS of PDGF-B/c-sis transcript and resultant efficient protein translation have been reported in only a few transformed cells and cultured umbilical vein endothelial cells. We have extended this knowledge to the developing rat brain, and suggest that a similar mechanism could operate widely in non-transformed tissue in vivo.

Primary sequences of rat mu-calpain large and small subunits are, respectively, moderately and highly similar to those of human.

cDNAs for rat mu-calpain large subunit and the calpain small subunit were cloned and sequenced. The large subunit encodes 713 amino-acid residues, which includes one deletion compared to that of human. The overall similarity is 89% to human mu-type, which is slightly lower than those compared between other types of calpain large subunits of rat and human (93-94%). On the other hand, the small subunit showed high conservation, being 94.0% identical to that of human. With these sequences, primary structures of all rat calpain subunits that have been considered to exist were completely elucidated.

Effects of recombinant human interleukin 1 alpha and interleukin 1 beta on cell growth and alkaline phosphatase of the mouse osteoblastic cell line MC3T3-E1.

Recombinant human interleukin 1 (rhIL-1)alpha and rhIL-1 beta were examined for their effects on DNA synthesis, cell growth and alkaline phosphatase activity of the mouse osteoblastic cell line MC3T3-E1. The relative activity of rhIL-1 alpha and rhIL-1 beta was compared in terms of the units which induced half-maximal [3H]thymidine uptake into mouse thymocyte cultures exposed to IL-1. Both rhIL-1 alpha and rhIL-1 beta significantly inhibited DNA synthesis and division of the cells in a concentration- and cultivation time-dependent fashion. In contrast, rhIL-1 alpha and rhIL-1 beta markedly increased alkaline phosphatase activity, which is a marker of osteoblastic differentiation. This activity in cells treated with rhIL-1 alpha and rhIL-1 beta increased about 2.0- and 1.7-fold, respectively, compared with that of control cultures. Inhibition of the DNA synthesis and stimulation of alkaline phosphatase activity by both types of rhIL-1 were completely neutralized by treatment with their respective polyclonal antisera. Also, inhibition of DNA synthesis was unaffected by the addition of cyclooxygenase and lipoxygenase inhibitors, and stimulation of alkaline phosphatase activity was unaffected by the addition of indomethacin. These results indicate that both rhIL-1 alpha and rhIL-1 beta have qualitatively similar biological effects on osteoblastic cells. They also suggest that IL-1 is an important modulator of the growth and differentiation of osteoblasts.

An Epstein-Barr virus-transformed B cell line produces autoregulatory interleukin-1 that regulates bone remodeling.

In this study, we demonstrate that an Epstein-Barr virus-transformed B cell line, A-11, produced interleukin-1 (IL-1), a cytokine that regulates bone remodeling. A-11 cells produce IL-1 in a cell dose- and culture time-related manner. The IL-1 activity was neutralized by recombinant human IL-1 (rhIL-1) alpha antiserum, but not by rhIL-1 beta antiserum. The IL-1 was semi-purified by (NH4)2SO4 precipitation, Superose prep 12 gel filtration, and anion-exchange chromatography strongly stimulated in vitro bone resorption. The stimulatory effect of the purified IL-1 on bone resorption was prostaglandin independent. Purified IL-1 inhibited DNA and collagen synthesis in the osteoblastic cell line MC3T3-E1. However, it enhanced significantly the cellular activity of alkaline phosphatase (EC 3.1.3.1), a marker enzyme for differentiation of osteoblasts. On the other hand, A-11 cell proliferation was inhibited by addition of rhIL-1 alpha antiserum, but not by rhIL-1 beta antiserum. And cell proliferation was stimulated by exogenous rhIL-1 alpha and -beta.

A randomised, placebo controlled clinical trial of the aldose reductase inhibitor CT-112 as management of corneal epithelial disorders in diabetic patients.

AIM: To evaluate the efficacy of topical aldose reductase inhibitor CT-112 (5-[3-ethoxy-4-pentyloxyphenyl]-2,4-thiazolidinedione) on corneal epithelial barrier function in diabetic patients. METHODS: This was a prospective, randomised, double masked placebo controlled study. 34 eyes of 34 diabetic patients were randomly assigned treatment with 0.25% eye drops of CT-112 (n = 22) or a placebo (n = 12) four times a day for 8 weeks. Corneal fluorescein staining and corneal sensation were examined before treatment as well as 4 and 8 weeks after administration. Corneal epithelial permeability to fluorescence was measured with an anterior fluorophotometer. RESULTS: Average scores of superficial punctate keratopathy and corneal sensitivity did not differ significantly between the two groups at any time. Whereas average fluorescein concentrations did not differ significantly for the CT-112 and placebo groups before treatment, they did differ significantly 4 and 8 weeks after treatment (4 weeks, p = 0.0327; 8 weeks, p = 0.0143). CONCLUSION: The topical aldose reductase inhibitor, CT-112 improves the corneal epithelial barrier function in diabetic patients.